# Interactions between Lipopolysaccharide and Peptide Bacteriocin BacSp222 Influence Their Biological Activities

## TL;DR

This study shows that LPS from Gram-negative bacteria and the peptide BacSp222 from a Gram-positive strain interact to reduce each other's biological effects in cells and insect larvae.

## Contribution

The novel finding is that LPS and BacSp222 form a complex through electrostatic interactions, which selectively reduces their pro-inflammatory and immune-stimulating activities.

## Key findings

- LPS and BacSp222 form a complex that reduces TNF and NO production in monocyte-macrophage cells.
- The complex lowers hemolymph phenoloxidase activity in larvae and inhibits BacSp222's antibacterial activity.
- Electrostatic interactions between LPS and BacSp222 decrease LPS aggregate size and form a direct complex.

## Abstract

This study describes the interactions between two different
pro-inflammatory
factors produced by bacteria, lipopolysaccharide (LPS) from Gram-negative
bacteria and the peptide BacSp222 produced by a Gram-positive zoonotic
strain, 222. We demonstrate that the mentioned molecules interact, forming
a complex, and this phenomenon selectively reduces their biological
activities in vitro and in vivo. Specifically, the levels of tumor
necrosis factor (TNF) and nitric oxide (NO) produced by monocyte-macrophage
cells were lower in samples treated with both LPS and BacSp222 compared
to those treated with LPS alone. This is most likely because BacSp222
limited the ability of LPS to stimulate the TLR4 receptor. In the larvae injected simultaneously
with LPS and BacSp222, the activity of hemolymph phenoloxidase, a
key component of the insect immune response, was lower than that observed
in larvae injected with either LPS or BacSp222 alone. Moreover, LPS
inhibited the antibacterial activity of the bacteriocin, while BacSp222
limited LPS’s ability to activate a proenzyme in the amebocyte lysate test. The changes in the
activities of BacSp222 and LPS were attributed to the electrostatic
interactions between LPS micelles and bacteriocin molecules, resulting
in a decrease in LPS aggregate size and the direct formation of a
complex between them, as revealed by gel filtration and isothermal
microcalorimetry.